It is known that FSH is required for the maturation of ovarian follicles and testicular spermatogenesis, and that, in adults, circulating FSH regulates gonadal differentiation and steroidogenesis. However, increases in ovarian follicle growth are not always correlated with elevations of FSH levels in circulating blood serum. It is also known that a particular ovarian follicle that is destined to ovulate is derived from a fairly large number of growing follicles which are, in turn, selected from a still larger group of nonproliferating primordial follicles formed during fetal development. As a result, it is concluded that there is some selection process by which, during each ovarian cycle, one of these follicles destined to ovulate is activated.
It has previously been postulated that there are proteins which suppress follicular response to gonadotropins such as FSH: diZerega et al., J. of Clin. Endocrinol. Metab., 56, 1, 35-41 (1983), J. of Clin. Endocrinol. Metab., 57, 4, 838-846 (1983), and J. of Clin. Endocrinol. Metab., 54, 6, 1091-1096 (1982). It was hypothesized by these investigators that the dominant follicle may be secreting a substance that suppressed the responses of the other follicles to the FSH: diZerega et al., J. Clin. Endocrinol. Metab., 56, 4, 147-155 (1983).
Further work in this area caused investigators to postulate that a protein, termed generically a follicle regulatory protein, was apparently present in a crude or partially purified extract from porcine follicular fluid which would delay follicular maturation and would inhibit the effects of FSH in some manner, Kling et al., Biology of Reproduction, 30, 564-572 (1984) and Ono et al., Am. J. Obstet. Gynecol., 154, 4, 709-716 (1986). Subsequently, U.S. Pat. Nos. 4,734,398 and 4,764,502 were issued directed to such extracts and stating that there were contained therein proteins between 5,500 and 18,000 daltons which exhibited such an effect. Although these partially purified extracts were useful for such in vitro studies, it is recognized that a pure material is necessary for clinical applications.